Eosinophil-associated Ribonuclease 11 Is a Macrophage Chemoattractant

Yamada, Kelsey J.; Barker, Tolga; Dyer, Kimberly D.; Rice, Tyler; Percopo, Caroline M.; Garcia-Crespo, Katia E.; Cho, Soochin; Lee, James J.; Druey, Kirk M.; Rosenberg, Helene F.

doi:10.1074/jbc.m114.626648

Cited by 14 publications

(22 citation statements)

References 66 publications

(69 reference statements)

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“…Yamada and colleagues [ 73 ] confirmed this finding, detecting expression of mEar 11 in alveolar macrophages challenged with Th2 cytokines ex vivo . Mouse Ear 11 was differentially expressed in somatic tissues at baseline, and its expression was augmented 10–1000-fold in response to administration of IL-33.…”

Section: Mouse Ear 11 Is Expressed In Response To Il-4 Il-13 Anmentioning

confidence: 72%

“…Of interest, Botos and colleagues [ 72 ] were the first to document the specific structural similarities between TLRs and ribonuclease inhibitor (RI), the latter a ring-shaped protein with strong affinity for RNase A-type ribonucleases. However, there are no reports of mEar2 or of any mEars promoting cytokine release from dendritic cells or any interactions indicating TLR2-dependence (see also [ 73 ]); given the species differences and sequence divergence, this is an important issue worthy of further consideration.…”

Section: Edn and Mear 2 Interact With Dendritic Cellsmentioning

confidence: 99%

“…( A ) Chemotactic indices calculated for leukocyte subsets, including Ly6G + (neutrophils), CD11c + F4/80 − (dendritic cells) and F4/80 + CD11c − (macrophages); * p < 0.05; ( B ) Representative flow plots documenting that F4/80 + CD11c − splenocytes (within boxes) from TLR2 −/− mice migrated in response to mEar 11 to an extent indistinguishable from those from wild-type mice. Reprinted from [ 73 ] with permission from American Society for Biochemistry and Molecular Biology.…”

Section: Future Directionsmentioning

confidence: 99%

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Eosinophil-Derived Neurotoxin (EDN/RNase 2) and the Mouse Eosinophil-Associated RNases (mEars): Expanding Roles in Promoting Host Defense

Rosenberg

2015

IJMS

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The eosinophil-derived neurotoxin (EDN/RNase2) and its divergent orthologs, the mouse eosinophil-associated RNases (mEars), are prominent secretory proteins of eosinophilic leukocytes and are all members of the larger family of RNase A-type ribonucleases. While EDN has broad antiviral activity, targeting RNA viruses via mechanisms that may require enzymatic activity, more recent studies have elucidated how these RNases may generate host defense via roles in promoting leukocyte activation, maturation, and chemotaxis. This review provides an update on recent discoveries, and highlights the versatility of this family in promoting innate immunity.

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Section: Mouse Ear 11 Is Expressed In Response To Il-4 Il-13 Anmentioning

confidence: 72%

Section: Edn and Mear 2 Interact With Dendritic Cellsmentioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

See 1 more Smart Citation

Eosinophil-Derived Neurotoxin (EDN/RNase 2) and the Mouse Eosinophil-Associated RNases (mEars): Expanding Roles in Promoting Host Defense

Rosenberg

2015

IJMS

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“…While barely missing the stringent cutoffs that we set for the RNA-seq analysis, qPCR analysis confirmed coregulation of Ear2, Ear11 , and Ear12 genes by the Akt-Acly pathway ( Figure 7E ). Ear genes are of interest because Ear2 and Ear11 are thought to have chemoattractant activity for dendritic cells and macrophages and are known to be highly induced in settings of Type 2 inflammation ( Cormier et al, 2002 ; Yamada et al, 2015 ). Therefore, the transcriptional profiling analysis indicated that the Akt-Acly pathway controls selective subsets of the M2 program to allow their modulation by metabolic input ( Figure 7—figure supplement 1A ).…”

Section: Resultsmentioning

confidence: 99%

Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation

Covarrubias

Aksoylar

et al. 2016

eLife

335

373

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Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts. How polarizing signals coordinate metabolic and functional reprogramming, and the potential implications for control of macrophage activation, remains poorly understood. Here we show that IL-4 signaling co-opts the Akt-mTORC1 pathway to regulate Acly, a key enzyme in Ac-CoA synthesis, leading to increased histone acetylation and M2 gene induction. Only a subset of M2 genes is controlled in this way, including those regulating cellular proliferation and chemokine production. Moreover, metabolic signals impinge on the Akt-mTORC1 axis for such control of M2 activation. We propose that Akt-mTORC1 signaling calibrates metabolic state to energetically demanding aspects of M2 activation, which may define a new role for metabolism in supporting macrophage activation.DOI: http://dx.doi.org/10.7554/eLife.11612.001

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“…Direct protein binding to TLR may occur ( 107 ) taking into account the striking shape similarity between the TLR receptor and the RNase inhibitor (RI), both of which have leucine-rich repeat (LRR) domains ( 150 ). Human RNase2 and mouse RNases2 are also both expressed in macrophages (Table 2 ) ( 48 , 107 ). Of note, the mouse eosinophil-associated RNase Ear11 works as a macrophage chemoattractant, although, in this case, the process is not directly mediated by TLR2 activation ( 48 , 107 ).…”

Section: The Rnase a Superfamilymentioning

confidence: 99%

Immune Modulation by Human Secreted RNases at the Extracellular Space

et al. 2018

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The ribonuclease A superfamily is a vertebrate-specific family of proteins that encompasses eight functional members in humans. The proteins are secreted by diverse innate immune cells, from blood cells to epithelial cells and their levels in our body fluids correlate with infection and inflammation processes. Recent studies ascribe a prominent role to secretory RNases in the extracellular space. Extracellular RNases endowed with immuno-modulatory and antimicrobial properties can participate in a wide variety of host defense tasks, from performing cellular housekeeping to maintaining body fluid sterility. Their expression and secretion are induced in response to a variety of injury stimuli. The secreted proteins can target damaged cells and facilitate their removal from the focus of infection or inflammation. Following tissue damage, RNases can participate in clearing RNA from cellular debris or work as signaling molecules to regulate the host response and contribute to tissue remodeling and repair. We provide here an overall perspective on the current knowledge of human RNases’ biological properties and their role in health and disease. The review also includes a brief description of other vertebrate family members and unrelated extracellular RNases that share common mechanisms of action. A better knowledge of RNase mechanism of actions and an understanding of their physiological roles should facilitate the development of novel therapeutics.

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Eosinophil-associated Ribonuclease 11 Is a Macrophage Chemoattractant

Cited by 14 publications

References 66 publications

Eosinophil-Derived Neurotoxin (EDN/RNase 2) and the Mouse Eosinophil-Associated RNases (mEars): Expanding Roles in Promoting Host Defense

Eosinophil-Derived Neurotoxin (EDN/RNase 2) and the Mouse Eosinophil-Associated RNases (mEars): Expanding Roles in Promoting Host Defense

Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation

Immune Modulation by Human Secreted RNases at the Extracellular Space

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